1. Field of the Invention
The present invention is generally related to a method for forming a nano-bubble, and more particularly to a method for forming a nano-bubble used in an ultrasound contrast agent.
2. Description of the Prior Art
An ultrasound contrast agent (UCA) is the substance to enhance image contrast in ultrasound imaging. Generally, it is micrometer-scaled encapsulating micro-bubbles injected into blood circulatory system via intravenous injection to enhance the reflection of the ultrasonic waves to thereby achieve the purpose of enhancing the resolution of ultrasound imaging.
After injected into veins, an ultrasound contrast agent (UCA) can change the ultrasonic characteristics of a tissue, such as backscatter coefficient, decay coefficient, sound velocity, and non-linear effect, to produce the imaging effect. The enhancement depends on the concentration and dimension of the ultrasound contrast agent and the frequency of ultrasonic radiation. The basic property of an ultrasound contrast agent is to enhance the backscatters of tissues to enhance the visibility and contrast of the ultrasonogram in ultrasound imaging. The non-linear effect produces harmonic generation with certain energy and the harmonic imaging technique can be used to measure the blood flow of a small vein and tissue perfusion and can suppress the noise generated by the motion of the tissue comprising no ultrasound contrast agent at the fundamental frequency. Thus, the signal-to-noise ratio can be greatly enhanced.
The research and application on the ultrasound contrast agent can be traced back to the initial observation of the contrast effect of a cloud of echoes after the intracardiac injection of saline in 1968 by Gramiak et al. In the late 80's, the ultrasonic tissue characterization has certain difficulties due to similar ultrasonic characteristics between some tissues even though these tissues are pathologically different. Thus, the ultrasound contrast agent that enhances the echogenicity of tissues and blood has drawn great attention.
The generation of the contrast agent is classified according to the type of gas filled in micro-bubbles where the first-generation contrast agent is mainly filled with air that is encapsulated by polymers like albumin or galactose; and the second-generation contrast agent is filled with high-density inert gas that is encapsulated by a soft thin membrane. Compared to the second-generation contrast agent, the membrane of the first-generation contrast agent is thicker and less elasticity and the filled gas is apt to dissolve in water and thus the micro-bubbles of the first-generation contrast agent tends to be broken and has a short lifetime. Therefore, the time for observation and diagnosis in the clinical application is limited. However, the diameter of the micro-bubble of the second-generation contrast agent is reduced to about 2-5 μm and the micro-bubble has longer stable time. Thus, the second-generation contrast agent has better vibration and backscatter characteristics.
In the past few years, the ultrasound contrast agent has been widely utilized in ultrasound therapy. Since the micro-bubbles in the ultrasound contrast agent can enhance cavitation effect to promote ultrasonic bio-effect. Therefore, the research of the ultrasound contrast agent on the direction of therapy like ultrasound thrombolysis, ultrasound-mediated gene delivery, and high intensity focused ultrasound (HIFU) has been taken off. Since the application area of the ultrasound contrast agent is continually expanded, the application value is greatly promoted. Therefore, it is important for the industry to continually develop an ultrasound contrast agent having high stability, controlled dimension, biodegradability, and biocompatibility.